Transport of Nanomedicine in the Environment

最近的研究估计，超过200种基于纳米技术的药物和输送系统已经进入临床前、临床或商业开发阶段，超过40种纳米药物产品已经上市，2011年纳米药物销售额估计达到200亿美元。随着纳米药物消费和生产的不断增加，人们越来越认识到纳米药物在环境中的发生和命运以及对人类健康的潜在后果。目前，填充治疗药物的聚合物纳米颗粒给药系统（PNDDS）是最常用的纳米药物形式之一，因为它们具有溶解水不溶性分子的能力，以及更高的有效载荷能力，延长血液循环时间，以及在水介质中优异的结构稳定性。虽然PNDDS的这些特性在制药科学方面是有益的，但从环境科学的角度来看，它可能是有害的，因为它促进了潜在生态危害的运输。因此，拟议工作的主要目标是更好地了解PNDDS在环境中的传输现象。智力价值：提议的活动主要旨在确定纳米药物在环境中运输过程中发生的扩散、对流、吸附、释放和降解过程的相对重要性。这项工作的另一个基本问题是确定这些过程如何不仅取决于纳米药物的结构和物理化学性质以及所涉及的环境表面，还取决于环境条件，如pH和温度。工作假设是，纳米药物在环境中的运输是由纳米药物性质（如尺寸和化学功能化）以及环境条件（如流速、温度、粗糙度和环境表面的化学性质）的协同组合调节的。该假设将通过石英晶体微平衡研究进行测试，使用模型环境表面，如二氧化硅、方解石和纤维素，以及具有不同尺寸、电荷、成分、负载特性和功能的各种类型的纳米药物。生成的数据将用环境运输模型来描述。PI在表面和界面科学、纳米技术和药物输送领域的独特专业知识使他能够产生有希望的初步结果，以支持项目的工作假设，并使他能够成功地管理这项工作。总的来说，从工程科学的角度来看，所提出的活性是重要的，因为它将促进对水环境中吸附表面附近纳米颗粒运输的认识和理解。这些知识对于正确评估纳米药物的分布和命运以及制定成功的战略以尽量减少其在环境中的扩散是至关重要的。该项目的成果也有望造福于其他领域和应用，这些领域和应用依赖于控制纳米颗粒和生物颗粒的吸附，如过滤、干影印、蛋白质和细胞分离，以及食品乳化和泡沫稳定。更广泛的影响：拟议的工作有三个组成部分，以整合研究和教育。第一部分努力增加代表性不足的学生在学术研究中的参与，第二部分涉及课程开发，第三部分涉及培养能够在学术或工业研究职位上成功地作为独立调查者的研究生。PI积极参与指导未被充分代表的本科生参与与所提议的工作直接相关的项目。透过这个计划，我们的目标是招募和培训更多少数族裔和未被充分代表的研究生和本科生，并向公众讲授纳米技术的环境方面。该项目还将为研究生提供环境科学、化学工程和纳米技术等多学科的培训。该研究成果将通过PI和学生在非正式的公众科学讲座、会议和部门研讨会上的演讲得到广泛传播。

1236532AkbulutRecent studies have estimated that more than 200 nanotechnology-based drugs and delivery systems have entered pre-clinical, clinical, or commercial development and over 40 nanomedicine products have been on the market, with nanomedicine sales estimated to have reached 20 billion dollars in 2011. With the increasing consumption and production of nanomedicine, the occurrence and fate of nanomedicine in the environment as well as the potential consequences for human health have been increasingly recognized. Currently, polymeric nanoparticulate drug delivery system (PNDDS) filled with therapeutic agents represents the one of the most commonly used forms of nanomedicine due to their ability to solubilize water-insoluble molecules as well as their higher payload capacity, extended blood circulation times, and excellent structural stability in aqueous media. While these properties of PNDDS are beneficial in terms of pharmaceutical science, it can be detrimental from that of environmental science, as it facilitates the transport of potential ecological hazards. The main objective of the proposed work is thus obtaining a better understanding of the transport phenomena of PNDDS in the environment.Intellectual Merit: The proposed activity primarily seeks to determine the relative importance of the diffusion, convection, adsorption, release, and degradation processes taking place during the transport of nanomedicine in the environment. Another fundamental issue in this work is determining how these processes depend not only upon the structural and physicochemical properties of the nanomedicine and the environmental surfaces involved but also upon environmental conditions such as pH and temperature. The working hypothesis is that the transport of nanomedicine in the environment is modulated by a synergistic combination of nanomedicine properties such as size and chemical functionalization as well as environmental conditions such as flow rates, temperature, roughness, and the chemistry of environmental surfaces. The hypothesis will be tested through quartz crystal microbalance studies using model environmental surfaces such as silica, calcite, and cellulose, as well as various types of nanomedicine with different sizes, charges, compositions, loading properties, and functionalities. The generated data will be described with environmental transport models. The PI's unique combination of expertise in surface and interface science, nanotechnology, and the drug delivery area has enabled him to generate promising preliminary results in the support of the project's working hypothesis and will allow him to successfully manage this work. Overall, the proposed activity is significant from an engineering science perspective, as it will advance knowledge and understanding of nanoparticle transport near adsorptive surfaces in aqueous environments. Such knowledge is critical to properly assess the distribution and fate of nanomedicine and to develop successful strategies for minimizing its dispersal in the environment. The outcomes of this project are also anticipated to benefit other fields and applications relying on controlling the adsorption of nanoparticles and bioparticles such as filtration, xerography, protein and cell separation, as well as food emulsion and foam stabilization.Broader Impact: The proposed work has three components for integrating research and education. The first component strives to increase the participation of underrepresented students in academic research, the second concerns curriculum development, and the third involves training graduate students who are capable of functioning successfully as independent investigators in academic or industrial research positions. The PI is actively involved in mentoring underrepresented undergraduate students in a project that is directly related to the proposed work. Through this project, we aim to recruit and train more minority and underrepresented graduate and undergraduate students and to teach the general public about the environmental aspects of nanotechnology. This project will also provide graduate students with multidisciplinary training in environmental science, chemical engineering, and nanotechnology. The work will be broadly disseminated through presentations by the PI and students at informal public science talks, conferences, and departmental seminars.